There has been a growing interest in the development and manufacturing of microscale fluid systems for the acquisition of chemical and biochemical information, in both preparative and analytical capacities. Adaptation of technologies from the electronics industry, such as photolithography, wet chemical etching and the like, has helped to fuel this growing interest.
One of the first areas in which microscale fluid systems have been used for chemical or biochemical analysis was in the area of capillary electrophoresis (CE). CE systems generally employ fused silica capillaries, or more recently, etched channels in planar silica substrates, filled with an appropriate separation matrix or medium. A sample fluid that is to be analyzed is injected at one end of the capillary or channel. Application of a voltage across the capillary then permits the electrophoretic migration of the species within the sample. Differential electrophoretic mobilities of the constituent elements of a sample fluid, e.g., due to their differential net charge or size, permits their separation, identification and analysis. In order to optimize the separation aspect of the CE applications, researchers have sought to maximize the electrophoretic mobility of charged species relative to each other and relative to the flow of the fluid through the capillary resulting from, e.g., electroosmosis. See, e.g., U.S. Pat. No. 5,015,350, to Wiktorowicz, and U.S. Pat. No. 5,192,405 to Petersen et al.
In comparison to these CE applications, the technologies of the electronics industry have also been focused on the production of small scale fluidic systems for the transportation of small volumes of fluids over relatively small areas, to perform one or more preparative or analytical manipulations on that fluid. These non-CE fluidic systems differ from the. CE systems in that their goal is not the electrophoretic separation of constituents of a sample or fluid, but is instead directed to the bulk transport of fluids and the materials contained in those fluids. Typically, these non-CE fluidic systems have relied upon mechanical fluid direction and transport systems, e.g., miniature pumps and valves, to affect material transport from one location to another. See, e.g., Published PCT Application No. 97/02357. Such mechanical systems, however, can be extremely difficult and expensive to produce, and still fail to provide accurate fluidic control over volumes that are substantially below the microliter range.
Electroosmotic (E/O) flow systems have been described which provide a substantial improvement over these mechanical systems, see, e.g., Published PCT Application No. WO 96/04547 to Ramsey et al. Typically, such systems function by applying a voltage across a fluid filled channel, the surface or walls of which have charged or ionizeable functional groups associated therewith, to produce electroosmotic flow of that fluid in the direction of the current. Despite the substantial improvements offered by these electroosmotic fluid direction systems, there remains ample room for improvement in the application of these technologies. The present invention meets these and other needs.
The present invention generally provides methods, systems and devices which provide for enhanced transportation and direction of materials using electroosmotic flow of a fluid containing those materials. For example, in a first aspect, the present invention provides methods of enhancing material direction and transport by electroosmotic flow of a fluid containing that material, which method comprises providing an effective concentration of at least one zwitterionic compound in the fluid containing the material.
In a related aspect, the present invention also provides methods of reducing electrophoretic separation of differentially charged species in a microscale fluid column, where that fluid column has a voltage applied across it, which method comprises providing an effective concentration of at least one zwitterionic compound in the fluid.
The present invention also provides microfluidic systems which incorporate these enhanced fluid direction and transport methods, i.e., provide for such enhanced fluid transport and direction within a microscale fluid channel structure. In particular, these microfluidic systems typically include at least three ports disposed at the termini of at least two intersecting fluid channels capable of supporting electroosmotic flow. Typically, at least one of the intersecting channels has at least one cross-sectional dimension of from about 0.1 xcexcm to about 500 xcexcm. Each of the ports may include an electrode placed in electrical contact with it, and the system also includes a fluid disposed in the channels, whereby the fluid is in electrical contact with those electrodes, and wherein the fluid comprises an effective concentration of a zwitterionic compound.